Molecular subtyping of ependymoma and prognostic impact of Ki-67

Autor: Ji Hoon Phi, Hyunhee Kim, Hongseok Yun, Jin-Woo Park, Ka Young Lim, Jeongwan Kang, Yumi Shim, Seung-Ki Kim, Sung Hye Park, Chun Kee Chung, Kwanghoon Lee, Chul-Kee Park, Jae Kyung Won
Rok vydání: 2021
Předmět:
Zdroj: Brain Tumor Pathology
ISSN: 1861-387X
1433-7398
DOI: 10.1007/s10014-021-00417-y
Popis: Although ependymomas (EPNs) have similar histopathology, they are heterogeneous tumors with diverse immunophenotypes, genetics, epigenetics, and different clinical behavior according to anatomical locations. We reclassified 141 primary EPNs from a single institute with immunohistochemistry (IHC) and next-generation sequencing (NGS). Supratentorial (ST), posterior fossa (PF), and spinal (SP) EPNs comprised 12%, 41%, and 47% of our cohort, respectively. Fusion genes were found only in ST-EPNs except for one SP-EPN with ZFTA-YAP1 fusion, NF2 gene alterations were found in SP-EPNs, but no driver gene was present in PF-EPNs. Surrogate IHC markers revealed high concordance rates between L1CAM and ZFTA-fusion and H3K27me3 loss or EZHIP overexpression was used for PFA-EPNs. The 7% cut-off of Ki-67 was sufficient to classify EPNs into two-tiered grades at all anatomical locations. Multivariate analysis also delineated that a Ki-67 index was the only independent prognostic factor in both overall and progression-free survivals. The gain of chromosome 1q and CDKN2A/2B deletion were associated with poor outcomes, such as multiple recurrences or extracranial metastases. In this study, we propose a cost-effective schematic diagnostic flow of EPNs by the anatomical location, three biomarkers (L1CAM, H3K27me3, and EZHIP), and a cut-off of a 7% Ki-67 labeling index. Supplementary Information The online version contains supplementary material available at 10.1007/s10014-021-00417-y.
Databáze: OpenAIRE
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